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CD3+CD56+ natural killer T (NKT)-like cells have an immune function of T cells and NK cells, which play an important role in antitumor and antiviral immune responses. This study aims to establish a CD3+CD56+ NKT-like cell model by simulating the memory NK effect induced by cytokines IL-12, IL-15, and IL-18 (IL-12/15/18) and explore the formation mechanism. Our study found that the IL-12/15/18 preactivated CD3+CD56+ NKT-like cells exhibited enhanced IFN-γ production in response to restimulation with IL-12/15/18 for 6h on day 7. The intrinsic potential of these trained cells was significantly improved, showing an increase in IFN-γ, TNF-α, and cell proliferation potential. The IFN-γ release, granzyme B level, and proliferation ability significantly increased when stimulated by NK-cell-sensitive K562 tumor cells. Among these cytokines, the combination of IL-12/15/18 was particularly effective. After the preactivation of IL-12/15/18, some cell surface proteins related to function and differentiation, such as CD11b, CD62 L, NKp46, NKG2A, and CD127, showed an evident and consistent change trend. The CDK4/6 inhibitor can effectively weaken this effect, and the expression of cyclin D1, Rb protein phosphorylation, and E2F-1 decreased significantly. Our work revealed that cytokine IL-12/15/18 can induce CD3+CD56+ NKT-like cells to obtain enhanced training immunity, which was a memory-like phenomenon. [ABSTRACT FROM AUTHOR]

Objective. This meta-analysis was performed to identify the prognostic value of SLNCR1 in multiple cancer types. Methods. Electronic databases, including PubMed, EMBASE, and Web of Science, Cochrane Library, Medline, BioMed Central, Springer, Science Direct, and China National Knowledge Internet (CNKI), were searched for relevant studies up to August 2021, and the hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to assess the relationship between SLNCR1 expression and overall survival (OS). Results. 12 studies with a total of 1155 patients with 9 different types of cancers were included in this meta-analysis. The pooled HR indicates that high SLNCR1 expression represented poorer prognosis of cancer (HR = 2.11, 95% CI: 1.59–2.80, I2 = 0%, P < 0.00001). Additionally, high SLNCR1 expression was correlated with TNM stage (odds ratio (OR): 1.72, 95% CI: 1.08–2.74, I2 = 62%, P = 0.02), lymph node metastasis (LNM) (OR:2.42, 95% CI: 1.61–3.64, I2 = 55%, P < 0.0001), and distant metastases (DM) (OR: 2.30, 95% CI: 1.50–3.55, I2 = 27%, P = 0.0002). However, no evidence was found for a relationship between SLNCR1 expression and clinical features such as tumor size (OR: 1.71, 95% CI: 0.93–3.14, I2 = 71%, P = 0.09), age (OR: 0.86, 95% CI: 0.68–1.08, I2 = 0%, P = 0.19), or gender (OR: 1.07, 95% CI: 0.64–1.81, I2 = 55%, P = 0.79). Conclusion. Our findings found that high SLNCR1 expression was associated with poor OS, advanced tumor stage, tumor size, LNM, and DM in multiple cancers, indicating that SLNCR1 may serve as a potential prognostic biomarker for cancer patients in China. [ABSTRACT FROM AUTHOR]